Network Hopping by PAK

The p21-activated kinases (PAKs) mediate the effects of Rho family proteins CDC42 and Rac on the actin cytoskeleton during processes such as cell migration. Cau et al. have now identified a PAK family member that modulates the microtubule (MT) network of cells as well. Ectopically expressed Xenopus PAK (X-PAK5) bound to newly formed MTs that nucleated from the centrosome of cultured Xenopus cells. Binding did not require X-PAK5 catalytic activity, and the interaction stabilized MTs, which appeared thick and curly. The X-PAK5-MT interaction also caused a pause in MT dynamics, where neither growth nor shrinkage occurred, a mechanism that could facilitate the development of a fully spread MT network. Overexpression of a constitutively active form of X-PAK5 caused a loss of the curly MT phenotype, but also induced cell-body retraction and the extension of numerous, actin-rich filipodia. In addition, constitutively activated X-PAK5 relocalized from MTs to actin-rich filopodia and lamellipodia. Although expression of constitutively active CDC42 or Rac did not activate X-PAK5, it caused a similar relocalization of X-PAK5 to actin-rich structure. Just how this PAK family member jumps from one cell structural network to another remains to be determined.